Project Summary/Abstract Craving and relapse are characteristic of drug and food addictions. A better understanding of what behavioral and neurobiological events underlie these behaviors could influence treatment approaches for addiction behaviors in general. We use an addiction model where rats self-administer (take) sucrose and then respond for a sucrose-paired cue (seek) when the sucrose is removed. We are interested in how the environment and passage of time since last having sucrose (abstinence) alters taking and seeking behaviors. We have found that environmental enrichment (EE) decreases taking and seeking, while abstinence increases both. The latter effect is known as ?incubation of craving? and it has been observed clinically for both drugs of abuse and food. Over the years of funding of this R15 we have conducted parametric evaluations of what environmental factors (e.g. social interaction, novelty) contribute to the EE effect. We have also tested the efficacy of behavioral (e.g. satiety) and pharmacological manipulations to reduce the incubation effect. Some of the pharmacological studies have targeted specific brain regions, and we have also evaluated changes in brain proteins following EE and/or abstinence. Recently, we found a large sex difference in sucrose taking and seeking. This R15 renewal proposal is to continue our successful line of research into the neurobiology of addiction, incorporating evaluation of sex differences. This proposal has 3 Aims. Aim 1 is to characterize sucrose taking in female and male rats, assessing primarily activational effects of sex hormones. Aim 2 compares males and females on sucrose taking and seeking following EE and/or abstinence from sucrose self-administration. Aim 3 also includes sex comparisons, and will examine the role of orbitofrontal cortex in the anti-seeking effect of EE. All of the work to be conducted will include undergraduate research assistants. This inclusion is a priority for the PI, and aligns with the objectives of the R15 mechanism. In addition, the work is of high quality and brings opportunities for undergraduates to gain experience in laboratory research at an institution where these opportunities are limited. Overall, these experiences will make it more feasible for students to pursue advanced training and careers in the biomedical and behavioral sciences.